Colon Cancer’s Cellular Crossroads

March 16, 2012 | Melissa Marino

Colon cancer development and progression involves alterations in several cell signaling pathways. Activation of the Wnt pathway is involved in the early stages of tumor development, while inactivation of signaling through the TGF-beta pathway (which typically suppresses tumor formation) is involved in later stages. However, the interactions between these pathways remain unclear.

R. Daniel Beauchamp, M.D., and colleagues investigated these interactions in human colorectal cancer samples, cell lines, and a mouse model of colon cancer. In a study published in the March issue of Gastroenterology, they show that reduced levels of Smad4 (a component of the TGF-beta pathway) correlated with increased levels of beta-catenin (a Wnt pathway component) in human colon cancers. In cell lines, depletion of Smad4 also increased beta-catenin and Wnt signaling. Similar interactions were found in intestinal tumors of mice.

The findings provide important information about the interaction among these signaling pathways, which could aid in assessing prognosis and identifying new therapeutic targets for colorectal cancer.